Terpenophenols

ABSTRACT

New terpenophenols of the general formula: ##STR1## wherein R is a 2-isobornyl, 5-camphyl or 2-norbornyl group of exo or endo configuration and in the ortho, meta or para position with respect to the OH group; R 1 , R 2  may each be a hydrogen atom or halogen atom (Cl, Br, F,I) or a lower alkyl or lower alkoxy radical having a straight or branched chain of 1 to 4 carbon atoms or a nitro or cyano group.

This is a division, of application Ser. No. 566,364, filed Apr. 9, 1975,now U.S. Pat. No. 4,067,899.

The present invention relates to new terpenophenols of the generalformula: ##STR2## in this formula: R is a terpene radical chosen fromthe following group: ##STR3## OF EXO OR ENDO CONFIGURATION AND IN THEORTHO, META OR PARA POSITION WITH RESPECT TO THE OH group.

R₁, r₂ may each be a hydrogen atom or halogen atom (Cl, Br, F, I) or alower alkyl or lower alkoxy radical having a straight or branched chainof 1 to 4 carbon atoms or a nitro or cyano group.

More particularly:

R is in the 2, 3 or 5 position of the phenol ring,

R₁ is a hydrogen atom or halogen atom, in particular Cl or Br, or anitro, cyano group or a lower alkyl or lower alkoxy radical having 1 to4 carbon atoms, in position 4 of the phenol ring.

R₂ is a hydrogen atom or a lower alkyl radical of 1 to 4 carbon atoms.

Advantageously, it is possible to prepare the terpenophenols of formula(I) in which R₁ is an atom of bromine by direction bromination of acorresponding terpenophenol (formula I, R₁ = H) by means of abromine-dioxan complex, in particular dioxan dibromide, preferably in anethyl ether medium, under cold conditions, at a temperature less than orequal to the ambient temperature in particular from 0° to 10° C.

Advantageously, it is possible to prepare the terpenophenols of formula(I) in which R₁ is a chlorine atom, by chlorination of the methyl etherof a corresponding terpenophenol (formula I, R₁ = H) by means ofphosphorus pentachloride, followed by demethylation of the resultingproduct. Demethylation may advantageously take place by means of redphosphorus in hydriodic acid.

These new phenols have interesting bacteriostatic properties and areuseful in the treatment of infections by gram + ve and gram - vebacteria. The following examples are given to illustrate the inventionwithout limiting the scope thereof.

EXAMPLE 1 2-isobornyl-4-nitro-5-methylphenol

0.7 cm³ of nitric acid (density 1.42g/cm³) are added dropwise to asolution, cooled to 15° C, of 2.4g of 2-isobornyl-5-methyl phenoldissolved in 15 cm³ of acetic acid. After the addition, the temperatureof the reaction mixture is maintained at 15° to 17° C for 3 hours thenthe mixture is left overnight at ambient temperature. The mixture ispoured on crushed ice, which is then extracted with ether, the etherealphase is washed with sodium carbonate and then with water. Afterevaporation under reduced pressure, a dark red viscous mass is obtainedwhich is dissolved in an 8:2 mixture of benzene/methanol andchromatographed on a silica gel column with the same mixture ofsolvents. There is thus obtained 0.8g of product which is crystallisedfrom cyclohexane. The pale yellow product obtained has a melting pointof 184°-186° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₃ NO₃ (M.W. = 289)

    ______________________________________                                                   C        H          N                                              ______________________________________                                        Calculated (%)                                                                             70.56      8.01       4.8                                        Found (%)    70.50      8.2        4.7                                        ______________________________________                                    

INFRA-RED SPECTRA

As a dispersion in KBr, the characteristic absorption bands are asfollows:

    ______________________________________                                        OH                 3360 cm.sup.-1                                             NO.sub.2           1530, 1320, 870, 640                                       Aromatic nucleus   1625, 1580, 1490                                           isobornyl          2950, 2890                                                 ______________________________________                                    

NUCLEAR MAGNETIC RESONANCE SPECTRA

The following peaks are observed for a solution in deuteratedchloroform, using tetramethyl silane (TMS) as reference.

    ______________________________________                                        CH.sub.3 (bridge head)                                                                             0.75 ppm      singlet                                    CH.sub.3 geminal     0.8 and 0.82 ppm                                                                            singlets                                   CH.sub.3 aromatic    2.55 ppm      singlet                                     ##STR4##                                                                              bornane ring (exo) aromatic                                                               1.65 ppm 3.15 ppm 6.7 and 8.1 ppm                                                           massive triplet singlets                   OH                   5.8 ppm                                                  ______________________________________                                    

EXAMPLE 2 2-isobornyl-4-bromo-5-methyl-phenol

3.06g of the dibromide of dioxan were added slowly with stirring to asolution, cooled to 5° C, of 30g of 2-isobornyl-5-methyl-phenol in 200cm³ of ethyl ether, whilst ensuring that the temperature of the reactionmixture does not exceed 10° C. After the addition, the mixture isallowed to return to ambient temperature and left overnight. The organicphase is washed successively with an aqueous solution of sodiumchloride, 10% sodium bicarbonate and finally water.

After drying and evaporation of the ether, the residue is crystallisedin pentane then in iso-octane and 21.4g of pure product are obtained(m.pt. 89°-90° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₃ OBr (M.W. = 322.9)

    ______________________________________                                                  C        H          Br                                              ______________________________________                                        Calculated (%)                                                                            63.18      7.12       24.74                                       Found (%)   63         7.2        24.5                                        ______________________________________                                    

I.R. SPECTRA

The following characteristic bands are observed with a 0.1 M solution inCCl₄ :

    ______________________________________                                        free OH           3.600 cm.sup.-1                                             aromatic nucleus  1615, 1505                                                  isobornyl         2850, 2880, 1470-1460                                       ______________________________________                                    

N.M.R. SPECTRA

The following peaks are observed with a solution in deuteratedchloroform (TMS reference):

    ______________________________________                                        CH.sub.3 Bridge head 0.78 ppm      singlet                                     ##STR5##                                                                              geminal (exo) aromatic                                                                    0.82 and 0.85 ppm 3.03 ppm 6.6 and 7.4                                                      singlets triplet singlets                  OH                   4.7 ppm                                                  ______________________________________                                    

EXAMPLE 3 2-isobornyl-4-nitrophenol

5.1 cm³ of nitric acid (d = 1.42) are added dropwise to a solution,cooled to 15° C, of 18.4g of O-isobornylphenol in 60 cm³ of acetic acid.After addition, the temperature of the reaction mixture is maintained at15° to 17° C for 5 hours and then the mixture is poured onto crushedice. It progressively forms a red viscous mass which is extracted, afterseparation of the aqueous phase, with 350 cm³ of ethyl ether. Theethereal solution is washed copiously with water than with 5% soda.

The alkaline phase is acidified and extracted with ether. Afterevaporation of the solvent and crystallisation of the residue inpetroleum ether (b.pt. 40°-65°), 10.5g of brown product are obtained(m.pt. 180°-182° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₆ H₂₁ NO₃ (M.W. = 275)

    ______________________________________                                                  C        H          N                                               ______________________________________                                        Calculated (%)                                                                            69.79      7.69       5.09                                        Found (%)   69.88      7.64       4.75                                        ______________________________________                                    

I.R. SPECTRA

In dispersion in KBr the following characteristic bands are observed:

    ______________________________________                                        NO.sub.2         1520, 1335, 860, 650 cm.sup.-1                               OH               3360                                                         aromatic nucleus 1620, 1590, 1485                                             isobornyl        2880-2950, 1460-1470                                         ______________________________________                                    

N.M.R. SPECTRA

The following major peaks are observed with a solution in deuteratedchloroform (TMS reference):

    ______________________________________                                        CH.sub.3 bridge head 0.8 ppm         singlet                                   ##STR6##                                                                              geminal (exo)                                                                             0.88 and 0.9 ppm 3.15 ppm 5.8 ppm                        ______________________________________                                                                             singlets triplet                     

EXAMPLE 4 2-isobornyl-4-bromophenol

10.8g of the dibromide of dioxane are added slowly with stirring to asolution, cooled to 5° C, of 10g of o-isobornyl-phenol in 100 cm³ ofethyl-ether while maintaining the temperature of the reaction between 5°and 10° C. After addition, the reaction mixture is allowed to reachambient temperature and left overnight. Then the mixture is washedsuccessively with a solution of sodium chloride, a 10% solution ofsodium bicarbonate then with water. The organic phase is dried and theether evaporated. The residue is distilled under reduced pressure. Thefraction which passes over at 183° C (at 3 mm Hg) is collected. Bycrystallisation in iso-octane, there is obtained 9g of pure, white,product, (m.pt. = 81° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₆ H₂₁ OBr (M.W. = 308.9)

    ______________________________________                                                  C        H          Br                                              ______________________________________                                        Calculated (%)                                                                            62.15      6.80       25.86                                       Found (%)   62.2       6.7        25.6                                        ______________________________________                                    

I.R. SPECTRA

In dispersion in KBr, the following characteristic bands are noted:

    ______________________________________                                        free OH           3560 cm.sup.-1                                              aromatic nucleus  1600, 1500, 890, 820                                        isobornyl         2880, 2950, 1470, 1480                                      ______________________________________                                    

N.M.R. Spectra

The following main peaks are observed with a solution in deuteratedchloroform (TMS reference)

    ______________________________________                                        CH.sub.3 bridge head 0.75 ppm        singlet                                   ##STR7##                                                                              geminal (exo)                                                                             0.8 and 0.82 ppm 3.05 ppm                                                                     singlets triplet                                              4.6 ppm                                                  ______________________________________                                    

EXAMPLE 5 2-exo-norbornyl-4-nitrophenol

3.8 ml. of nitric acid (d = 1.42) were added dropwise to a solution,cooled to 15° C, of 9.4g of o-exo-norbornylphenol in 20 cm³ of aceticacid. After the addition the temperature of the reaction mixture ismaintained at 15° - 17° C for 3 hours, and is then left for 3 days at atemperature of 5° C. The mixture is then poured on crushed ice, theaqueous phase is decanted and the precipitated brown viscouse mass isextracted with ether. The solvent is removed under reduced pressure andcrystallization of the residue in cyclohexane gives 2.4g of pure,grey-white, product (m.pt. 134° - 136° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₃ H₁₅ NO₃ (M.W. = 233)

    ______________________________________                                                  C        H          N                                               ______________________________________                                        Calculated (%)                                                                            66.93      6.48        6.01                                       Found (%)   66.88      6.50        5.90                                       ______________________________________                                    

I.R. SPECTRA

In dispersion of KBr, the following characteristic absorption bands arenoted:

    ______________________________________                                        NO.sub.2          1520, 1330, 650 cm.sup.-1                                   OH                3360 cm.sup.-1                                              aromatic nucleus  1620, 1590, 1500                                            norbornyl         2880, 2960                                                  ______________________________________                                    

N.M.R. SPECTRA

In deuterated chloroform the following main peaks are observed (TMSreference).

    ______________________________________                                         ##STR8##   (exo)     1.6 ppm 2.9 ppm 5.9 ppm                                                                     massive triplet                           ______________________________________                                    

EXAMPLE 6 2-isocamphyl-4-bromophenol

8.6g of the dibromide of dioxan are added with stirring to a solution,cooled to 5° C, of 8g of O-isocamphylphenol in 50 cm³ of ethyl etherwhilst ensuring that the temperature of the reaction media does notexceed 10° C. The mixture is then left to reach ambient temperature andleft overnight.

The ethereal phase is washed successively with a solution of sodiumchloride, 10% sodium bicarbonate, sodium chloride and finally withwater. The organic phase is then dried over magnesium sulphate and theother is removed under reduced pressure. The residue is crystallised iniso-octane and after three crystallisations there is obtained 2g of pureproduct (m.pt 67° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₆ H₂₁ Br O (M.W. = 309.25)

    ______________________________________                                                  C        H          Br                                              ______________________________________                                        Calculated (%)                                                                            62.1       6.8        25.9                                        Found (%)   62.7       6.8        25.7                                        ______________________________________                                    

I.R. SPECTRA

In dispersion of KBr, the following characteristic bands are noted:

    ______________________________________                                        isocamphyl          2900, 2950 cm.sup.-1                                      aromatic nucleus    1600, 1500, 820                                           OH                  3605 (in CC14)                                            ______________________________________                                    

N.M.R. SPECTRA

In deuterated chloroform, the following peaks are observed (TMSreference).

    ______________________________________                                        Isocamphyl CH.sub.3     0.85 ppm     doublet                                             CH.sub.3 geminal                                                                           0.9 and 1 ppm                                                                              singlets                                 OH                      5 ppm                                                 ______________________________________                                    

EXAMPLE 7 2-isobornyl-4-chloro-5-methylphenol

In a three necked flask fitted with a condenser, there is introduced51.7g (0.2 mole) of 2-isobornyl-5-methylanisole and 41.6g (0.2 mole) ofphosphorus pentachloride. The mixture is heated to 110°-115° C for 2hours, then the phosphorus trichloride formed is distilled at reducedpressure and the reaction mass is poured into iced water. An extractionwith ether is undertaken, the organic phase is washed with water untilneutral, dried on sodium sulphate and the ether is evaporated. An orangecrystalline mass is obtained. By crystallization in ethanol, 44.2g of2-isobornyl-4-chloro-5-methylanisole are obtained (m.pt 71°-73° C).

A mixture of 0.003 moles of red phosphorus, 18g of a solution of 57%hydriodic acid (d = 1.70) acetic acid and 0.04 moles of the productobtained previously, is heated to reflux during 30 minutes and heated atreflux during 17 hours. After reaction, the mixture is filtered on glasswool, dissolved in water and extracted with ether. The organic phase iswashed with a solution of sodium carbonate, then water and dried oversodium sulphate. After evaporation of the solvent, there is obtained anoil which is crystallised in pentane then in iso-octane. There is thusobtained 5.3g of pure product (m.pt. = 98°-100° C).

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₃ Cl O (M.W. = 278.8)

    ______________________________________                                                  C        H          Cl                                              ______________________________________                                        Calculated (%)                                                                            73.4       8.3        13                                          Found (%)   73.6       8.25       12.8                                        ______________________________________                                    

I.R. SPECTRA

In dispersion in KBr, the following characteristic bands are observed:

    ______________________________________                                        isobornyl          2880, 2959, cm.sup.-1                                      aromatic nucleus   1615, 1510, 860                                            OH                 3540                                                       ______________________________________                                    

N.M.R. SPECTRA

The following peaks are observed with a solution in deuteratedchloroform (TMS reference):

    ______________________________________                                        CH.sub.3                                                                             bridge head 0.79 ppm        singlet                                    CH.sub.3                                                                             geminal     0.82-0.88 ppm   singlets                                   CH.sub.3                                                                             aromatic    2.2 ppm                                                    H      aromatic    6.5 and 7.2 ppm                                            OH     phenol      4.5 ppm                                                    ______________________________________                                    

EXAMPLE 8 ##STR9## 2-EXO-NORBORNYL-4-BROMOPHENOL

53g of dioxan dibromide (0.21 mole) are added slowly for 15 minutes to asolution, cooled to 0° C, of 40g 2-exo-norbornyl phenol (0.21 mole) in200 cm³ ethyl ester. After stirring at ambient temperature for 1 hour,the ethereal phase is washed successively with a solution of sodiumchloride, then a solution of sodium bicarbonate and then with wateruntil neutral. It is then dried on sodium sulphate, evaporated undervacuum and then distilled at reduced pressure. The fraction B.P.₁ = 150°C is recovered and 35g of a colourless oil, which forms a mass, areobtained.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₃ H₁₅ OBr (M.W. = 267.17)

    ______________________________________                                                    C        H        Br                                              ______________________________________                                        Calculated                                                                              (%)     58.44      5.66   29.91                                     Found     (%)     58.20      5.52   29.90                                     ______________________________________                                    

I.R. SPECTRA

In the form of a film, the following characteristic bands are noted:

    ______________________________________                                        norbornyl       2870, 2950, 1475 cm.sup.-1                                    OH              3550, 3440 cm.sup.-1                                          ______________________________________                                    

N.M.R. SPECTRA

The following peaks are observed with a solution in dimethyl sulfoxide(TMS reference):

    ______________________________________                                        norbornyl  endo proton                                                                              2.9 ppm       triplet                                              other protons                                                                            1.5 ppm       massive                                   OH                    9.5 ppm       singlet                                   aromatic nucleus      6.7-7.10-7.15 ppm                                       ______________________________________                                    

EXAMPLE 9 ##STR10## 2-EXO-NORBORNYL-4-BROMO-5-METHYLPHENOL

100g of dioxan dibromide (0.4 mole) are added slowly to a solution,cooled to 0° C, of 80g 2-exo-norbornyl-5-methylphenol (0.4 mole) in 400cm³ anhydrous ether, whilst ensuring that the temperature does notexceed 5° C. After stirring for 1 hour, the ethereal phase is washedsuccessively with a solution of sodium chloride, then a solution ofsodium bicarbonate and then with water until neutral. It is then driedon sodium sulphate and the solvent is evaporated under vacuum. Theresidue is crystallised in pentane at -20° C. 82g of a pure product areobtained (m.pt = 80° C.)

ANALYTICAL CHARACTERISTICS

Analysis for C₁₄ H₁₇ OBr (M.W. = 281.20)

    ______________________________________                                                    C        H        Br                                              ______________________________________                                        Calculated                                                                              (%)     59.80      6.08   28.42                                     Found     (%)     59.91      6.00   28.57                                     ______________________________________                                    

I.R. SPECTRA

In dispersion in KBr, the main absorption bands are as follows:

    ______________________________________                                        norbornyl        2950, 2870, 1455 cm.sup.-1                                   OH               3200 cm.sup.-1                                               aromatic nucleus 1615, 1500 cm.sup.-1                                         ______________________________________                                    

N.M.R. SPECTRA

In solution in dimethyl sulfoxide the following main peaks are observed(TMS reference)

    ______________________________________                                        norbornyl   CH.sub.2                                                                              1.4 ppm        massive                                                H endo  2.35 ppm       triplet                                    OH                  9.38 ppm       singlet                                    aromatic protons    6.72 - 7.15 ppm                                           CH.sub.3            2.2 ppm        singlet                                    ______________________________________                                    

EXAMPLE 10 ##STR11## 2-EXO-NONBORNYL-4-CHLOROPHENOL

120g 2-exo-norbornyl anisole (0.59 mole) and 135g phosphoruspentachloride (0.65 mole) are heated to 100° C for 2 hours, then thephosphorus trichloride formed is distilled at reduced pressure. It isthen poured into iced water and extracted with chloroform. The organicphase is washed with a solution of sodium bicarbonate, then with wateruntil neutral. After having driven off the solvent, it is distilled atreduced pressure and the fraction B.P₀.2 = 120° C is recovered. 95g of acolourless oil are thus obtained. which oil is2-exo-norbornyl-4-chloroanisole.

4g red phosphorus, 200 cm³ hydriodic acid and 400 cm³ acetic acid areheated at 100° C for 30 minutes under nitrogen. After cooling to 20° C,the oil previously obtained is added and the mixture is heated to 100° -110° C, under nitrogen for 24 hours. Filtration is then carried out on"Celite 545" and the filtrate is poured into 1 liter of water. Themixture is extracted with methylene chloride, washed in water, dried onsodium sulphate and the solvent is driven off. The product is distilledat reduced pressure and the fraction R.P.₀.1 = 122° C is recovered. 55gof a colourless oil are obtained.

ANALYTIC CHARACTERISTICS

Analysis for C₁₃ H₁₅ OCl (M.W. = 222.72)

    ______________________________________                                                   C        H         Cl                                              ______________________________________                                        Calculated                                                                             (%)     70.11      6.79    15.92                                     Found    (%)     70.20      6.67    15.83                                     ______________________________________                                    

I.R. SPECTRA

Recorded in the form of a film, the spectrum comprises the followingcharacteristic bands:

    ______________________________________                                        norbornyl        2960, 2880, 1480 cm.sup.-1                                   OH               3550, 3440                                                   aromatic nucleus 1610, 1500, 815                                              ______________________________________                                    

N.M.R. SPECTRA

In solution in CDCl₃, the following peaks are observed (TMS reference):

    ______________________________________                                        norbornyl     CH.sub.2                                                                              1.5 ppm       massive                                                 H endo  2.8 ppm       triplet                                   OH                    5 ppm                                                   aromatic protons      6.65-7-7.15 ppm                                         ______________________________________                                    

EXAMPLE 11 ##STR12## 2-ISOBORNYL-4-CHLOROPHENOL

80g 2-isobornyl anisole (0.33 mole) and 76g phosphorus pentachloride(0.36 mole) are heated at 120° C for 2 hours. The PCl₃ formed is thendistilled under vacuum and the reaction mixture is poured into icedwater. The mixture is extracted with ether, the organic phase is washedwith water until neutral, dried on sodium sulphate and the ether isevaporated. 90g of a red oil (2-isobornyl-4-chloroanisole) are obtained.

4g red phosphorus, 200 cm³ hydriodic acid and 500 cm³ acetic acid areheated under reflux for 30 minutes. After cooling to 20° C, the oilpreviously obtained is added and the mixture is heated under reflux,under nitrogen, for 24 hours. After cooling, the insoluble matter isseparated by filtration and the filtrate is poured into 1 liter ofwater. The mixture is extracted with ether, washed with a solution ofsodium thiosulphate and then with water until neutral. After drying onsodium sulphate, the ether is evaporated and the product is distilled atreduced pressure. The fraction B.P.₀.1 = 150° C is recovered. After twocrystallizations from pentane, 18g of pure product are obtained. M.P. =86°-87° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₆ H₂₁ OCl (M.W. = 264.80)

    ______________________________________                                                    C        H        Cl                                              ______________________________________                                        Calculated                                                                              (%)     75.28      7.99   13.39                                     Found     (%)     72.65      7.86   13.28                                     ______________________________________                                    

I.R. SPECTRA

In solution in CDCl₃, the following characteristic bands are noted:

    ______________________________________                                        isobornyl 2960, 2860, 1480, 1460, 1380, 1370 cm.sup.-1                        OH        3600 cm.sup.-1                                                      ______________________________________                                    

N.M.R. SPECTRA

In CDCl₃, the following peaks are observed (TMS reference):

    ______________________________________                                        isobornyl  CH.sub.3                                                                             bridge head                                                                             0.75 ppm   (s)                                               CH.sub.3                                                                             geminal   0.80-0.85 ppm                                                                            (s)                                               H      endo      3.05 ppm   triplet                                OH                          5 ppm                                             aromatic protons            6.6-6.45-7.25 ppm                                 ______________________________________                                    

EXAMPLE 12 ##STR13## 2-METHYL-4-METHOXY-5-ISOBORNYL PHENOL

19g of 85% meta-perchlorobenzoic acid are added, with stirring, atambient temperature to a solution of 20g 2-methyl-4-methoxy-5-isobornylbenzaldehyde in 150 cm³ anhydrous methylene chloride. After stirring for30 minutes, the mixture is filtered and the filtrate is washed with asolution of sodium bicarbonate, then with a solution of sodiumbisulphite and finally with water. After drying on sodium sulphate, thesolvent is evaporated, the residue taken up in 150 cm³ methanol 150 cm³10N soda are added and stirring is carried out for 10 minutes afterwhich the mixture is acidified with concentrated HCl. One extracts withmethylene chloride and then washes with water until neutral. Afterdrying on sodium sulphate and evaporation of the solvent, the residue iscrystallized twice from iso-octane and 10.5g of pure product areobtained. m.p. = 120° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₈ H₂₆ O₂ (M.W. = 274.39)

    ______________________________________                                                    C        H        O                                               ______________________________________                                        Calculated                                                                              (%)     78.79      9.55   11.66                                     Found     (%)     78.90      9.50   11.60                                     ______________________________________                                    

I.R. SPECTRA

In solution in CCl₄, the following characteristic bands are noted:

    ______________________________________                                        isobornyl     2950, 2880, 1470, 1460 cm.sup.-1                                --O--CH.sub.3 --                                                                            2830 cm.sup.-1                                                  ______________________________________                                    

N.M.R. SPECTRA

In solution in CDCl₃, the following peaks are observed (TMS reference):

    ______________________________________                                        isobornyl                                                                              CH.sub.3 bridge head                                                                              0.65 ppm  (s)                                             CH.sub.3 geminal    0.80 ppm  (s)                                             H        endo       3.2 ppm   triplet                                --O-- CH.sub.3 --            3.72 ppm  (s)                                    OH                           4.6 ppm   (s)                                    CH.sub.3 aromatic            2.2 ppm   (s)                                    H        aromatic            6.55-6.7 ppm                                     ______________________________________                                    

EXAMPLE 13 ##STR14## 2-ISOCAMPHYL-4-METHYLPHENOL

1080g para-cresol (10 moles) and 680g camphene (5 moles) are dissolvedin 2 liters of nitromethane. Whilst cooling to 0° C, there is added insmall portions 450g aluminum chloride, whilst ensuring that thetemperature does not exceed 5° C. It is then left for one night in therefrigerator. One then washes several times with water, dries themixture on sodium sulphate and evaporates the nitromethane under vacuum.One then distills under reduced pressure and the fraction B.P₃ = 160° -165° C is recovered, which is crystallized from iso-octane. 210g of pureproduct are obtained. M.P. = 75°-76° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₄ O (M.W. = 244.36)

    ______________________________________                                                    C        H         O                                              ______________________________________                                        Calculated                                                                               (%)    83.55      9.90    6.55                                     Found     (%)     83.42      9.96    6.62                                     ______________________________________                                    

I.R. SPECTRA

In solution in CCl₄, the following bands are noted:

    ______________________________________                                        isocamphyl                                                                             :     2950, 2860, 1470, 1450, 1365, 1375 cm.sup.-1                   OH       :     3600                                                           ______________________________________                                    

N.M.R. SPECTRA

    ______________________________________                                        isocamphyl                                                                            CH.sub.3 0.85 ppm             doublet                                         CH.sub.3 geminal  0.87 - 1 ppm                                                H        endo     2.9 ppm     triplet                                 CH.sub.3                                                                              aromatic          2.17 ppm                                            H       aromatic          6.7 - 6.85 ppm                                      OH                        8.8 ppm     (s)                                     ______________________________________                                    

EXAMPLE 14 ##STR15## 3-ISOBORNYL-4-METHOXYPHENOL

8g of 85% m-perchlorobenzoic acid are added at ambient temperature andwith stirring to a solution of 8g (0.03 mole) 3-isobornyl-4-methoxybenzaldehyde in 70 cm³ anhydrous methylene chloride. After stirring for2 hours, one filters and washes the organic phase with a solution ofpotassium bicarbonate, then with water. After drying, the solvent isevaporated and the residue is taken up in 50 cm³ methanol and 5 cm³ sodalye. One leaves it in contact for 30 minutes, then acidifies with HCl,dilutes with 200 cm³ water and extracts with ether. The ethereal phaseis washed with water and then the ether is driven off. The residue isdissolved in benzene and the solution is poured onto a 50g silicacolumn. One elutes with 300 cm³ benzene, evaporates the solvent andcrystallizes from iso-octane. 3.8g of pure product are thus obtained.M.P. = 98° - 100° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₄ O₂ (M.W. = 260.36)

    ______________________________________                                                    C        H        O                                               ______________________________________                                        Calculated                                                                              (%)     78.42      9.29   12.29                                     Found     (%)     78.35      9.40   12.25                                     ______________________________________                                    

I.R. SPECTRA

In solution in CCl₄, the following bands are noted:

    ______________________________________                                        isobornyl    :        2950, 2880 cm.sup.-1                                    O - CH.sub.3 -                                                                             :        2820, 1230, 1050                                        OH           :        3608 cm.sup.-1                                          ______________________________________                                    

N.M.R. SPECTRA

In solution in CDCl₃, the following peaks are observed (TMS reference):

    ______________________________________                                        isobornyl   CH.sub.3                                                                              bridge head 0.65 ppm (s)                                              CH.sub.3                                                                              geminal     0.78 ppm (s)                                  --O-- CH.sub.3                  3.70 ppm (s)                                  OH                              5.42 ppm (s)                                  aromatic protons                6.75 ppm (m)                                  ______________________________________                                    

EXAMPLE 15 ##STR16## 2-ISOBORNYL-4-CYANO-5-METHYLPHENOL

14.5g (0.05 mole) of 2-methyl-4-methoxy-5-isobornyl benzaldehyde areheated under reflux for 18 hours with 5g hydroxylamine hydrochloride, 6gsodium acetate and 150 cm³ acetic acid. After evaporation the residue istaken up in benzene. The solution obtained is poured onto a 100g columnof silica. It is eluted with 350 cm³ benzene and after evaporation, 9g2-methyl-4-methoxy-5-isobornyl benzonitrile are obtained. M.P. = 110° C.

The preceding product is heated with 90g pyridine hyrochloride for 6hours to 220°-225° C. The mixture which is still hot is poured into 1liter of water and the unsoluble substance formed is recovered byfiltration. After washing with water and drying, one crystallizes from abenzene - iso-octane mixture (7:3) and 7.5g of pure product are thusobtained. M.P. = 200° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₈ H₂₃ O N (M.W. = 269.37)

    ______________________________________                                                    C        H         N                                              ______________________________________                                        Calculated                                                                              (%)     80.25      8.61    5.20                                     Found     (%)     80.35      8.48    5.25                                     ______________________________________                                    

I.R. SPECTRA

In solution in chloroform, the following main bands are noted:

    ______________________________________                                        isobornyl    :        2960, 2880 cm.sup.-1                                    OH           :        3595, 3300 cm.sup.-1                                    CN           :        2225 cm.sup.-1                                          ______________________________________                                    

N.M.R. SPECTRA

In solution in a CDCl₃ - DMSO mixture the following peaks are observed.(TMS reference)

    ______________________________________                                        isobornyl  :     CH.sub.3                                                                             bridge head                                                                           0.75 ppm   (s)                                           :     CH.sub.3                                                                             geminal 0.82 - 0.87 ppm                                                                          (s)                                aromatic nucleus                                                                         :     CH.sub.3       2.38 ppm   (s)                                protons    :                    6.75 - 7.42 ppm                                          :     OH             9.42 ppm                                      ______________________________________                                    

EXAMPLE 16 ##STR17## 2-ISOBORNYL-4-CYANO PHENOL

9g 3-isobornyl-4-methoxy benzaldehyde (0.033 mole) are heated underreflux for 20 hours with 3g hydroxylamine hydrochloride (0.043 mole), 3gsodium acetate and 90 cm³ acetic acid. The insoluble matter is separatedby filtration, the solvent is evaporated and the residue taken up inseveral cubic centimeters of benzene and the solution is poured onto a100g column of silica. One elutes with 400 cm³ benzene, then evaporatesthe solvent and crystallizes the residue form iso-octane. 5.6 g of3-isobornyl-4-methoxy benzonitrile are thus obtained. M.P. = 98° - 100°C.

The preceding product is heated under nitrogen to 220° C for 4 hourswith 56g pyridine hydrochloride. The mixture, which is still hot, ispoured into 300 cm³ water. The insoluble matter is recovered byfiltration, washed with water, dried and crystallized from a mixture ofbenzene and iso-octane (7:3) then from benzene. 2.1g of a pure productare obtained. M.P. = 173° C.

ANALYTICAL CHARACTERISTICS

Analysis for C₁₇ H₂₁ O N (M.W. = 355.35)

    ______________________________________                                                     C        H         N                                             ______________________________________                                        Calculated                                                                              (%)      79.96      8.29    5.49                                    Found     (%)      80.12      8.37    5.38                                    ______________________________________                                    

I.R. SPECTRA

In dispersion in KBr, the following main bands are noted:

    ______________________________________                                        isobornyl      :       2950, 2880 cm.sup.-                                    aromatic nucleus                                                                             :       1510, 1610, cm.sup.-1                                  CN             :       2240 cm.sup.-1                                         OH             :       3260 cm.sup.-1                                         ______________________________________                                    

N.M.R. SPECTRA

In solution in a CDCl₃ - DMSO mixture, the following peaks are observed(TMS reference)

    ______________________________________                                        isobornyl  CH.sub.3                                                                              bridge head                                                                              0.74 ppm   (s)                                             CH.sub.3                                                                              geminal    0.80-0.83 ppm                                                                            (s)                                  aromatic nucleus   OH         9.5 ppm                                         protons                       6.9-7.3-7.5 ppm                                 ______________________________________                                    

BACTERIOSTATIC ACTIVITY

The bacteriostatic activity of the phenols according to the inventionhas been evaluated by the method of streaks in gelose media. This methodcomprises making increasing dilutions of the product to be tested, innutritive geloses poured into a Petri dish.

The various bacteria to be studied are then introduced onto the gelosesin parallel streaks by means of a platinum loop which has been immersedin a 24 hour old culture of each bacteria.

The bacteriostatic amount corresponds to the weakest concentration forwhich the bacteria does not develop along the striation.

The activity of these compounds has been studied vis a vis two gram + vebacteria, namely Staphylococcus Aureus and Streptococcus Pyrogenes.

The following table shows the minimum inhibitory concentrations,expressed in mg/liter, of the products described in the examples.

MINIMAL INHIBITORY CONCENTRATION mg/liter

    ______________________________________                                        Product of                                                                            Staphylococcus                                                                             Streptococcus                                                                              Escherichia                                 example Aureus       Pyrogenes    Coli                                        ______________________________________                                        1       1            7.5                                                      2       5            15                                                       3       1            5                                                        4       2            30                                                       5       5            10                                                       6       2.5          5                                                        7       2.5          5                                                        8       7.5          20           7.5                                         9       5                         20                                          10      5                         10                                          11      2.5          10                                                       12      5                                                                     13      5            20                                                       14      5            10                                                       15      5            10                                                       16      5            7.5                                                      ______________________________________                                    

TOXICITY

The LD 50 of the compounds of the invention, determined in the mouse andrat is greater than 1000 mg/kg.

The products according to the invention may be used as anti-infectiousagents. To this end, they may be made in a suitable form for oral orrectal administration, such as tablets, capsules, suppositories having adose of 100 - 200 mg active ingredient to be administered at the rate of200 mg - 1,000 mg. per day.

What is claimed is:
 1. A terpenophenol of formula ##STR18## in which Ris 2-exonorbornyl, R₂ is H or methyl and R₁ is chlorine or bromine.
 2. Aterpenophenol according to claim 1 which is2-exo-norbornyl-4-bromo-5-methylphenol.
 3. A terpenophenol according toclaim 1 which is 2-exo-norbornyl-4-bromophenol.
 4. A terpenophenolaccording to claim 1 which is 2-exo-norbornyl-4-chlorophenol.